AB0114 INCREASED EXPRESSION OF SEMAPHORIN 4A IN SYSTEMIC LUPUS ERYTHEMATOSUS AND ITS ASSOCIATION WITH THE ACTIVITY OF LUPUS NEPHRITIS
Authors: Y. Choi, E. K. Lee, K. M. Kim, M. S. Lee, C. H. Lee, C. H. Chung, W. H. Yoo
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Semaphorin (SEMA), initially identified as a neural guidance molecule, has been recently highlighted for its role in regulating the immune response. Among seven categories of SEMA, Class 4A SEMA (SEMA4A) involves the T cell-mediated immune responses through the expression of itself in dendritic cells. <h3>Objectives</h3> This study aimed to investigate the expression of SEMA4A in systemic lupus erythematosus (SLE) and the association between the expression of SEMA4A and the activity of lupus in the lupus mouse model and patients with SLE. <h3>Methods</h3> The expression of SEMA4A was measured from peripheral blood mononuclear cells (PBMCs) in healthy controls and patients with SLE by polymerase chain reaction. Bone marrow-derived dendritic cells (BMDCs) and renal tissues from control mice and Toll-like receptor (TLR)-7 agonist (R848)-induced lupus mice were investigated for the expression of SEMA4A using western blotting and immunofluorescence assay. Immunohistochemistry was performed to examine the expression of SEMA4A in the kidney of the patients with SLE and they were analyzed according to the activity index of lupus nephritis. <h3>Results</h3> The expression of SEMA4A of PBMCs was elevated in the patients with SLE (n=20, 3.86±0.80) compared to those of healthy control (n=20, 1.0±0.37). SEMA4A is constitutively expressed by dendritic cells, so we analyzed the expression of SEMA4A in BMDCs of TLR-7 agonist (R848)-induced lupus murine group and control group. The SEMA4A was highly expressed in the BMDCs of the lupus group (2.06±1.67) compared to the control group (1.0±0.29). The immunocytochemistry also showed enhanced fluorescence intensity of SEMA4A in BMDCs of the lupus mouse group (19.57±1.37) compared to the control group (10.43±1.87). The kidneys, one of the main target organs of SLE, were analyzed for the protein level of SEMA4A in the murine lupus group and control group. The western blotting of the whole kidney and isolated glomeruli showed a marked expression of SEMA4A in the lupus group compared to the control group. The mean fluorescence intensity of SEMA4A in the kidneys of lupus mice was significantly enhanced compared to the control group (8.51±0.47 Vs. 3.75 ±0.13). In the analysis of immunohistochemistry of SEMA4A in the kidneys of the patients with SLE, the positivity of SEMA4A staining was markedly higher in lupus nephritis with higher activity score (≥10) (80%) compared to those of lupus nephritis with lower activity score (&lt;10) (0%). <h3>Conclusion</h3> The expression of SEMA4A is significantly increased in the dendritic cells and kidneys of the lupus murine group and the patients with SLE compared to the control group. The expression of SEMA4A in the kidneys in the patients with SLE correlates with the severity of lupus nephritis. These results indicate the possible contribution of SEMA4A in the pathogenesis of SLE and the potential of targeting SEMA4A for the treatment of SLE. <h3>Reference</h3> [1]Nishide M, Kumanogoh A. The role of semaphorins in immune responses and autoimmune rheumatic diseases. Nat Rev Rheumatol. 2018 Jan;14(1):19-31. doi: 10.1038/nrrheum.2017.201. Epub 2017 Dec 7. PMID: 29213125. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.